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A Study to Investigate the Recovery, Excretion and Pharmacokinetics of [14C]-GSK2140944 Administered as a Single Intravenous and Single Oral Dose to Healthy Adult Male Subjects

2017년 7월 10일 업데이트: GlaxoSmithKline

An Open-Label, Non-Randomized, Two-Period, Cross-Over, Mass Balance Study to Investigate the Recovery, Excretion and Pharmacokinetics of 14C-GSK2140944 Administered as a Single Intravenous and Single Oral Dose to Healthy Adult Male Subjects (BTZ115774)

This is an open-label, non-randomized, two-period, cross-over, mass balance study that will evaluate the recovery, excretion, and pharmacokinetics of a single intravenous (IV) dose of [14C]-GSK2140944 (Period 1) and a single oral dose of [14C]-GSK2140944 ( Period 2) in 6 healthy male subjects. The results from this study will aid in the design of future clinical pharmacology studies such as the thorough corrected QT interval study, special population studies (renal, hepatic, critically ill patients), potential drug interaction studies, and will help to establish safe and efficacious intravenous and oral dosing regimens.

연구 개요

연구 유형

중재적

등록 (실제)

6

단계

  • 1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

      • London, 영국, NW10 7NS
        • GSK Investigational Site

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

30년 (성인)

건강한 자원 봉사자를 받아들입니다

연구 대상 성별

남성

설명

Inclusion Criteria:

  • A subject will be eligible for inclusion in this study only if all of the following criteria apply:
  • Male aged between 30 and 55 years of age inclusive, at the time of signing the informed consent.
  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests and cardiac monitoring.
  • A subject with a clinical abnormality or laboratory parameter outside the reference range for the population being studied may be included only if the Investigator feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Body weight >=50 kilogram and Body Mass Index within the range 19- 31 kilogram per square meter (inclusive).
  • Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and bilirubin <=1.5xupper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • A history of regular bowel movements (averaging one or more bowel movements per day).
  • Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Protocol. This criterion must be followed from the time of the first dose of study medication until four months after the last dose.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >21 units for males. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 ml) of beer, 1 glass (125 milliliter [mL]) of wine or 1 (25 mL) measure of spirits.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy must be excluded.
  • History of sensitivity to quinolones including photosensitivity and tendon rupture.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening or positive test for Human Immunodeficiency Virus (HIV) antibody.
  • A screening or Day -1 urinalysis positive for protein or glucose (greater than "1+" findings of protein or glucose).
  • A serum creatinine value between screening and Day -1 visit that is increased by more than 0.2 milligrams per decilitre (or 15.25 micromole per liter) changes.
  • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • A positive pre-study drug/alcohol screen.
  • Exclusion criteria for screening and baseline ECG (a single repeat is allowed for eligibility determination): Heart rate <40 and >100 beats per minute; PR Interval <120 and >220 milliseconds (msec); QRS duration <70 and >100 msec; QT duration corrected for heart rate by Bazett's formula (QTcB) or QT duration corrected for heart rate by Fridericia's formula (QTcF) interval >450 msec; Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization); Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular block [second degree or higher], Wolf Parkinson White [WPW] syndrome), sinus pauses> 3 seconds, non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual subject.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 millilitre (mL) within a 56 day period.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Subjects who have received a total body radiation dose of greater than 5.0 millisievert (upper limit of World Health Organization category II) or exposure to significant radiation (e.g. serial x-ray or CT scans, barium meal etc) in the 12 months prior to this study.

  • Any condition that could interfere with the accurate assessment and recovery of radioactivity [14C].
  • Participation in a clinical trial involving administration of 14C-labelled compound(s) within the last 12 months.
  • Unwillingness to commit to avoid excessive exposure to sunlight (or exposure whilst on a tanning bed) which would cause a sunburn reaction from first dose up to and including discharge.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위화되지 않음
  • 중재 모델: 크로스오버 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: GSK2140944 for Injection and Capsule
Each subject will receive a single 1000 milligram (mg) IV dose of GSK2140944 containing [14C]-GSK2140944 of approximately 22.5 microcurie [μCi] (approximately 0.8 megabecquerel [MBq]) of radioactivity given as a 2 hour infusion on Day 1 of treatment period 1 and 2000 mg oral dose of GSK2140944 containing [14C]-GSK2140944 of approximately 45 μCi (approximately 1.7 MBq) of radioactivity on Day 1 of treatment period 2. Each treatment period will be followed with washout of atleast 8 Days.
GSK2140944 (1 gram) for Injection will be supplied as powder for injection containing [14C] GSK2140944. Non sterile powder is to be dissolved aseptically in sterile water for injection to a concentration of 4 mg/mL free base equivalent. IV solution is prepared by sterile filtration. 250 mL of IV solution, equivalent to 1000 mg GSK2140944, is then administered intravenously.
GSK2140944 Capsule (2 gram) will be supplied as powder in capsule containing [14C] GSK2140944. Powder is to be filled in empty capsule to achieve 200-400 mg strength per capsules as free base equivalent. Sufficient capsules are administered to provide the required total dose of 2 gram as free base.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
GSK2140944 PK parameters following single IV or oral doses of [14C]-GSK2140944
기간: Pre-dose and post dose(0 minute [min], 15 min, 30 min, 60 min, 120 min, 2.5 hour[hr], 3 hr, 4 hr, 6 hr, 6.5 hr, 8 hr, 12 hr, 16 hr, 24 hr, 48 hr, 72hr, 96 hr, 120hr, 144 hr, 168 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr and 168 hr) of each treatment period
From the plasma concentration-time and blood/plasma radioactivity concentration-time data, the following pharmacokinetic parameters will be determined, as data permit: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-t) and AUC(0-∞)], and apparent terminal phase half-life (t1/2). Systemic clearance (CL) and volume of distribution (Vdss) of GSK2140944 may be calculated for IV regimen only.
Pre-dose and post dose(0 minute [min], 15 min, 30 min, 60 min, 120 min, 2.5 hour[hr], 3 hr, 4 hr, 6 hr, 6.5 hr, 8 hr, 12 hr, 16 hr, 24 hr, 48 hr, 72hr, 96 hr, 120hr, 144 hr, 168 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr and 168 hr) of each treatment period
Total recovery of radioactivity in urine and feces following separate single IV and oral doses of [14C]-GSK2140944
기간: Pre-dose and post dose(0-6 hr, 6 12 hr, 12 24 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr, 168 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr and 168 hr) of each treatment period
Total recovery of radioactivity in urine and feces is defined as a percentage of total radioactive dose in each interval and cumulatively.
Pre-dose and post dose(0-6 hr, 6 12 hr, 12 24 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr, 168 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr and 168 hr) of each treatment period

2차 결과 측정

결과 측정
측정값 설명
기간
Number of subjects with adverse events (AE)
기간: Up to 7 weeks
Up to 7 weeks
Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by concomitant medications review
기간: Up to 7 weeks
Up to 7 weeks
Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by clinical laboratory tests
기간: Day 1 and Day 8 of each treatment period
clinical laboratory tests includes hematology, clinical chemistry, urinalysis
Day 1 and Day 8 of each treatment period
Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by electrocardiogram (ECG)
기간: Day 1 (Pre dose and 1 hr, 2 hr, 4 hr and 8 hr post dose)and Day 8 of each treatment period
Single 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT interval (QTc) intervals.
Day 1 (Pre dose and 1 hr, 2 hr, 4 hr and 8 hr post dose)and Day 8 of each treatment period
Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by vital signs
기간: Day 1 (Pre dose and 1 hr, 2 hr, 4 hr and 8 hr post dose)and Day 8 of each treatment period
Vital sign measurements to be measurement include systolic and diastolic blood pressure, pulse rate and temperature.
Day 1 (Pre dose and 1 hr, 2 hr, 4 hr and 8 hr post dose)and Day 8 of each treatment period

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2013년 11월 8일

기본 완료 (실제)

2013년 11월 30일

연구 완료 (실제)

2013년 11월 30일

연구 등록 날짜

최초 제출

2013년 11월 7일

QC 기준을 충족하는 최초 제출

2013년 11월 27일

처음 게시됨 (추정)

2013년 12월 4일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2017년 7월 13일

QC 기준을 충족하는 마지막 업데이트 제출

2017년 7월 10일

마지막으로 확인됨

2017년 7월 1일

추가 정보

이 연구와 관련된 용어

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

IPD 계획 설명

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

연구 데이터/문서

  1. 주석이 달린 사례 보고서 양식
    정보 식별자: 115774
    정보 댓글: For additional information about this study please refer to the GSK Clinical Study Register
  2. 임상 연구 보고서
    정보 식별자: 115774
    정보 댓글: For additional information about this study please refer to the GSK Clinical Study Register
  3. 개별 참가자 데이터 세트
    정보 식별자: 115774
    정보 댓글: For additional information about this study please refer to the GSK Clinical Study Register
  4. 통계 분석 계획
    정보 식별자: 115774
    정보 댓글: For additional information about this study please refer to the GSK Clinical Study Register
  5. 정보에 입각한 동의서
    정보 식별자: 115774
    정보 댓글: For additional information about this study please refer to the GSK Clinical Study Register
  6. 연구 프로토콜
    정보 식별자: 115774
    정보 댓글: For additional information about this study please refer to the GSK Clinical Study Register
  7. 데이터 세트 사양
    정보 식별자: 115774
    정보 댓글: For additional information about this study please refer to the GSK Clinical Study Register

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

GSK2140944 for Injection에 대한 임상 시험

3
구독하다